A Phase II feasibility study of oral etoposide given concurrently with radiotherapy followed by dose intensive adjuvant chemotherapy for children with newly diagnosed high-risk medulloblastoma (protocol POG 9631)

A report from the Children's Oncology Group

Adam J. Esbenshade, Mehmet Kocak, Linda Hershon, Pierre Rousseau, Jean Claude Decarie, Susan Shaw, Peter Burger, Henry S. Friedman, Amar Gajjar, Albert Moghrabi

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background: Children with high-risk medulloblastoma historically have had a poor prognosis. The Children's Oncology Group completed a Phase II study using oral etoposide given with radiotherapy followed by intensive chemotherapy. Procedure: Patients enrolled in the study had high-risk disease defined as ≥1.5 cm2 of residual disease postsurgery or definite evidence of central nervous metastasis. All patients underwent surgery followed by radiotherapy. During radiation, the patients received oral etoposide (21 days on, 7 off) at an initial dose of 50 mg/m2 per day (treatment 1), which was reduced to 35 mg/m2 per day (treatment 2) due to toxicity. After radiotherapy, the patients received chemotherapy with three cycles of cisplatin and oral etoposide, followed by eight courses of cyclophosphamide and vincristine. Results: Between November 1998 and October 2002, 53 patients were accrued; 15 received treatment 1 and 38 treatment 2. Forty-seven patients (89%) were eligible. Response to radiation was excellent, with 19 (40.4%) showing complete response, 24 (51.1%) partial response, and four (8.5%) no recorded response. The overall 2- and 5-year progression-free survival (PFS) was 76.6 ± 6% and 70.2 ± 7%, respectively. The 2- and 5-year overall survival (OS) was 80.9 ± 6% and 76.6 ± 6%, respectively. Clinical response postradiation and PFS/OS were not significantly different between the treatment groups. There was a trend toward a difference in 5-year PFS between those without and with metastatic disease (P = 0.072). Conclusions: Oral etoposide was tolerable at 35 mg/m2 (21 days on and 7 days off) when given during full-dose irradiation in patients with high-risk medulloblastoma with encouraging survival data.

Original languageEnglish (US)
Article numbere26373
JournalPediatric Blood and Cancer
Volume64
Issue number6
DOIs
StatePublished - Jun 1 2017

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Medulloblastoma
Feasibility Studies
Etoposide
Adjuvant Chemotherapy
Radiotherapy
Disease-Free Survival
Survival
Radiation
Therapeutics
Drug Therapy
Vincristine
Cyclophosphamide
Cisplatin
Neoplasm Metastasis

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

Cite this

A Phase II feasibility study of oral etoposide given concurrently with radiotherapy followed by dose intensive adjuvant chemotherapy for children with newly diagnosed high-risk medulloblastoma (protocol POG 9631) : A report from the Children's Oncology Group. / Esbenshade, Adam J.; Kocak, Mehmet; Hershon, Linda; Rousseau, Pierre; Decarie, Jean Claude; Shaw, Susan; Burger, Peter; Friedman, Henry S.; Gajjar, Amar; Moghrabi, Albert.

In: Pediatric Blood and Cancer, Vol. 64, No. 6, e26373, 01.06.2017.

Research output: Contribution to journalArticle

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title = "A Phase II feasibility study of oral etoposide given concurrently with radiotherapy followed by dose intensive adjuvant chemotherapy for children with newly diagnosed high-risk medulloblastoma (protocol POG 9631): A report from the Children's Oncology Group",
abstract = "Background: Children with high-risk medulloblastoma historically have had a poor prognosis. The Children's Oncology Group completed a Phase II study using oral etoposide given with radiotherapy followed by intensive chemotherapy. Procedure: Patients enrolled in the study had high-risk disease defined as ≥1.5 cm2 of residual disease postsurgery or definite evidence of central nervous metastasis. All patients underwent surgery followed by radiotherapy. During radiation, the patients received oral etoposide (21 days on, 7 off) at an initial dose of 50 mg/m2 per day (treatment 1), which was reduced to 35 mg/m2 per day (treatment 2) due to toxicity. After radiotherapy, the patients received chemotherapy with three cycles of cisplatin and oral etoposide, followed by eight courses of cyclophosphamide and vincristine. Results: Between November 1998 and October 2002, 53 patients were accrued; 15 received treatment 1 and 38 treatment 2. Forty-seven patients (89{\%}) were eligible. Response to radiation was excellent, with 19 (40.4{\%}) showing complete response, 24 (51.1{\%}) partial response, and four (8.5{\%}) no recorded response. The overall 2- and 5-year progression-free survival (PFS) was 76.6 ± 6{\%} and 70.2 ± 7{\%}, respectively. The 2- and 5-year overall survival (OS) was 80.9 ± 6{\%} and 76.6 ± 6{\%}, respectively. Clinical response postradiation and PFS/OS were not significantly different between the treatment groups. There was a trend toward a difference in 5-year PFS between those without and with metastatic disease (P = 0.072). Conclusions: Oral etoposide was tolerable at 35 mg/m2 (21 days on and 7 days off) when given during full-dose irradiation in patients with high-risk medulloblastoma with encouraging survival data.",
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T1 - A Phase II feasibility study of oral etoposide given concurrently with radiotherapy followed by dose intensive adjuvant chemotherapy for children with newly diagnosed high-risk medulloblastoma (protocol POG 9631)

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AU - Esbenshade, Adam J.

AU - Kocak, Mehmet

AU - Hershon, Linda

AU - Rousseau, Pierre

AU - Decarie, Jean Claude

AU - Shaw, Susan

AU - Burger, Peter

AU - Friedman, Henry S.

AU - Gajjar, Amar

AU - Moghrabi, Albert

PY - 2017/6/1

Y1 - 2017/6/1

N2 - Background: Children with high-risk medulloblastoma historically have had a poor prognosis. The Children's Oncology Group completed a Phase II study using oral etoposide given with radiotherapy followed by intensive chemotherapy. Procedure: Patients enrolled in the study had high-risk disease defined as ≥1.5 cm2 of residual disease postsurgery or definite evidence of central nervous metastasis. All patients underwent surgery followed by radiotherapy. During radiation, the patients received oral etoposide (21 days on, 7 off) at an initial dose of 50 mg/m2 per day (treatment 1), which was reduced to 35 mg/m2 per day (treatment 2) due to toxicity. After radiotherapy, the patients received chemotherapy with three cycles of cisplatin and oral etoposide, followed by eight courses of cyclophosphamide and vincristine. Results: Between November 1998 and October 2002, 53 patients were accrued; 15 received treatment 1 and 38 treatment 2. Forty-seven patients (89%) were eligible. Response to radiation was excellent, with 19 (40.4%) showing complete response, 24 (51.1%) partial response, and four (8.5%) no recorded response. The overall 2- and 5-year progression-free survival (PFS) was 76.6 ± 6% and 70.2 ± 7%, respectively. The 2- and 5-year overall survival (OS) was 80.9 ± 6% and 76.6 ± 6%, respectively. Clinical response postradiation and PFS/OS were not significantly different between the treatment groups. There was a trend toward a difference in 5-year PFS between those without and with metastatic disease (P = 0.072). Conclusions: Oral etoposide was tolerable at 35 mg/m2 (21 days on and 7 days off) when given during full-dose irradiation in patients with high-risk medulloblastoma with encouraging survival data.

AB - Background: Children with high-risk medulloblastoma historically have had a poor prognosis. The Children's Oncology Group completed a Phase II study using oral etoposide given with radiotherapy followed by intensive chemotherapy. Procedure: Patients enrolled in the study had high-risk disease defined as ≥1.5 cm2 of residual disease postsurgery or definite evidence of central nervous metastasis. All patients underwent surgery followed by radiotherapy. During radiation, the patients received oral etoposide (21 days on, 7 off) at an initial dose of 50 mg/m2 per day (treatment 1), which was reduced to 35 mg/m2 per day (treatment 2) due to toxicity. After radiotherapy, the patients received chemotherapy with three cycles of cisplatin and oral etoposide, followed by eight courses of cyclophosphamide and vincristine. Results: Between November 1998 and October 2002, 53 patients were accrued; 15 received treatment 1 and 38 treatment 2. Forty-seven patients (89%) were eligible. Response to radiation was excellent, with 19 (40.4%) showing complete response, 24 (51.1%) partial response, and four (8.5%) no recorded response. The overall 2- and 5-year progression-free survival (PFS) was 76.6 ± 6% and 70.2 ± 7%, respectively. The 2- and 5-year overall survival (OS) was 80.9 ± 6% and 76.6 ± 6%, respectively. Clinical response postradiation and PFS/OS were not significantly different between the treatment groups. There was a trend toward a difference in 5-year PFS between those without and with metastatic disease (P = 0.072). Conclusions: Oral etoposide was tolerable at 35 mg/m2 (21 days on and 7 days off) when given during full-dose irradiation in patients with high-risk medulloblastoma with encouraging survival data.

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